The control of potassium excretion in the body depends largely on the functional properties of the distal tubule and cortical collecting tubule. Most of the K+ filtered by the kidney is reabsorbed by the proximal tubule and by the loop of Henle. However, depending on the metabolic situation, the distal nephron either reabsorbs or secretes potassium. The data necessary for a precise decription of K+ transport across the distal nephron, namely the apical and basolateral membrane potentials and conductances, the intracellular ion activities and the paracellular conductances are lacking because of the difficulty of impaling mammalian distal nephron cells with microelectrodes. The aims of this study are, 1) to develop a new isolated distal tubule preparation in which stable electrical potential and ion activity measurements can be made, 2) to characterize the mechanism of K+ transport at the level of the cell membrane in the Amphiuma isolated late distal tubule, and 3) to determine how these transport mechanisms are affected by the major modulators of distal K+ transport. Electro-physiological techniques will be employed to determine the net flux of K+, the total and K+ conductances of the cell membranes and the shunt and the transepithelial and transmembrane electrochemical driving forces for K+ transport. The contribution of the paracellular versus cellular pathway in net potassium transport and the relative importance of active versus passive pathways will be assessed. Having defined these parameters, the effects of modulators of K+ transport, such as K+ adaptation and acid-base distrubances will be studied with particular attention given to the identification of the site and mechanism of action of these modulators.